Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free...

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YIA-CL-1 Subcutaneous Tissue Biopsy is a Useful Diagnostic and Prognostic Tool for Cardiac Amyloidosis YASUHIRO IZUMIYA, SEIJI TAKASHIO, MEGUMI YAMAMURO, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Cardiac involvement in systemic amyloidosis causes detrimental prog- nosis, therefore early detection and classification are important to develop appropri- ate therapeutic strategies. Subcutaneous tissue biopsy is a useful screening for systemic amyloidosis; however, its diagnostic and prognostic value in patients with cardiac amyloidosis remains elusive. Methods: We retrospectively analyzed 14 con- secutive patients with cardiac amyloidosis who underwent subcutaneous tissue bi- opsy. Results: Amyloid deposition was observed in 11 patients (79%). Histopathological analysis demonstrated that acquired monoclonal immunoglobulin light-chain amyloidosis could be predicted when the degree of amyloid deposition was greater in blood vessels than adipose tissue compare to senile systemic amyloid- osis and familial amyloidosis (60% vs. 0%; p50.03). During the follow-up period (median 297 days, range 3-761 days), 7 patients died or were admitted to the hospital due to worsening heart failure. Among them, 6 patients (86%) were positive for am- yloid deposition in blood vessels. The incidence of death and composite outcome, in- cluding heart failure hospitalization and death, was significantly higher in patients positive for amyloid deposition in blood vessels than in those without (p50.03, p50.006; respectively). Conclusions: Amyloid subtype could be diagnosed by ana- lyzing the degree of amyloid deposition in blood vessels and adipose tissue using subcutaneous tissue biopsy samples in patients with cardiac amyloidosis. Amyloid deposition in blood vessels suggests poor prognosis of these patients. YIA-CL-2 Preoperative Levels of Bilirubin or Creatinine Adjusted by Age can Predict Their Reversibility After Implantation of Left Ventricular Assist Device TERUHIKO IMAMURA 1 , KOICHIRO KINUGAWA 2 , TARO SHIGA 1 , TOSHIRO INABA 1 , HISATAKA MAKI 1 , MASARU HATANO 1 , ATSUSHI YAO 1 , SHUNEI KYO 2 , MINORU ONO 3 , RYOZO NAGAI 4 1 Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2 Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 3 Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 4 Jichi Medical University, Tochigi, Japan Background: To predict a reversibility of end-organ function after LVAD implanta- tion is difficult in patients with decompensated state, but is indispensable to determin- ing the eligibility for transplant listing. Methods and Results: Preoperative data were obtained from 69 patients with LVAD (18 continuous-flow, 51 pulsatile). Persis- tent hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or cre- atinine (Cre) more than 1.5 mg/dL at 6 months after LVAD implantation. TB score or Cre score was calculated: 0.15 Age + 1.1 (preoperative TB) or 0.2 Age + 3.6 (preoperative Cre), in which coefficients were determined on the basis of odds ra- tios for persistent hepatic or renal dysfunction, respectively. ROC analyses showed good predictabilities for persistent end-organ dysfunction (AUCs: 0.794 for the TB score and 0.839 for the Cre score). Using the combination of both scores, 6 months’ mortality by multiple organ failure was significantly stratified into 3 groups: the low (5.6%, the TB score !11.0 with any Cre score), intermediate (22.2%, the TB score O11.0 but the Cre score !14.1), and high (83.3%, the TB score O11.0 and the Cre score O14.1) risk strata. Conclusions: Reversibility of end-organ function with LVAD can be predicted by our new risk scoring system, which is beneficial in strat- ifying the likelihood of transplant listing during bridge to candidacy. YIA-CL-3 Cardiac Troponin T Release is Increased by Coronary Microvascular Dysfunction in Patients with Nonischemic Heart Failure SEIJI TAKASHIO, MEGUMI YAMAMURO, YASUHIRO IZUMIYA, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Background: Cardiac troponin T (cTnT) is established as a specific biomarker of on- going myocardial damage and predicts adverse outcome in patients with heart failure (HF). However, the mechanisms of underlying cTnT release remain unclear. It is re- ported that coronary microvascular dysfunction is potential cause for elevated cTnT release. Therefore, we evaluated the association between coronary microvascular dysfunction and cTnT release from failing myocardium by novel highly sensitive as- say. Methods and Results: We studied 45 nonischemic HF patients (mean age: 62615 y.o, Male: 69 %, ejection fraction: 42.5611.5 %). Coronary flow reserve (CFR) was calculated by using a intracoronary Doppler guidewire (FloWire, Volcano, Rancho Cordova, CA, U.S.A.) and CFR ! 2.0 was considered existing coronary mi- crovascular dysfunction. Serum cTnT levels sampled from aortic root (Ao) and cor- onary sinus (CS) simultaneously during cardiac catheterization were measured. cTnT extracted from heart was describe as the differences between Cs and Ao of cTnT levels (d cTnT). CFR ! 2.0 was observed in 14 patients (31%). d cTnT levels of CFR ! 2.0 patients were significantly higher than those of CFR O and 5 2.0 pa- tients (6.767.5 ng/L vs. 2.261.8 ng/L; p50.047). Conclusions: cTnT release into coronary circulation was increased by existing coronary microvascular dysfunction in nonischemic HF patients. Coronary microvascular dysfunction is considered one of the causes for elevated cTnT. YIA-CL-4 Prognostic Impact of Increased Heart Rate on Heart Failure with Preserved Ejection Fraction TSUYOSHI TAKADA 1 , YASUHIKO SAKATA 2 , SATOSHI MIYATA 2 , JUN TAKAHASHI 1 , KOTARO NOCHIOKA 1 , MASANOBU MIURA 1 , HIROAKI SHIMOKAWA 1 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2 Department of Evidenced-Based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Since heart failure (HF) with preserved ejection fraction (HFpEF) is generally complicated with diastolic dysfunction, it is anticipated that heart rate (HR) control is crucial for the management of HFpEF as compared with HF with re- duced EF (HFrEF). Thus, we examined the influence of HR control on cardiovascular (CV) mortality in patients with HFpEF and those with HFrEF. Methods: Among the 10,219 patients in our cohort, as named CHART-2 Study, we enrolled 2,978 patients with Stage C/D HF and sinus rhythm (mean age 67.8 years, 69.0% male). CV mor- tality during the median follow-up period of 3.1 years was compared among the fol- lowing 4 groups; G1 (n51121, HR!71bpm, EF$50%), G2 (n5853, HR$71bpm, EF$50%), G3 (n5491, HR!71bpm, EF!50%), and G4 (n5513, HR$71bpm, EF!50%). Results: G2 had a significantly higher CV mortality than G1 (6.0 vs. 3.6%, P50.009), whereas G3 and G4 had similar CV mortality (10.0 vs. 9.9%, P50.740). A Cox regression analysis revealed that G2 was associated with signifi- cantly higher CV mortality than G1 (hazard ratio 1.79, P50.008), whereas G3 showed comparable prognosis to G4 (hazard ratio 0.85, P50.418). Conclusions: These results indicate that increased HR is associated with worse prognosis in pa- tients with HFpEF but not in those with HFrEF, suggesting that HR could be a ther- apeutic target for HEpEF but not for HFrEF. YIA-CL-5 Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free Survival after Acute Myocardial Infarction MASAHIKO HARA 1 , YASUHIKO SAKATA 1,2 , SEN MATSUMOTO 1 , MASAYA USAMI 1 , SHINICHIRO SUNA 1 , DAISAKU NAKATANI 1 , ISSEI KOMURO 1 1 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan, 2 Department of Cardiovascular Medicine and Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), in- cluding docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocar- dial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. Methods and Results: We evaluated whether serum DHA and EPA levels were as- sociated with HF-free survival, and HF hospitalization rates after AMI. We enrolled 712 AMI patients and divided them into 3 groups (Low, Middle, and High) according to the tertilevalues of DHA or EPA serum levels. Impact of serum n-3 PUFA levels was assessed using propensity-score-stratified Cox regression analysis. Although both DHA and EPA Low groups showed statistically significant worse HF-free sur- vival as compared to other groups (HR 1.68, p50.0358 in DHA and HR 1.69, p50.0280 in EPA), only EPA Low group had a higher risk of HF hospitalization (HR 2.40, p50.0097). Unfavorable impacts of low DHA or EPA levels were gener- ally common in all subgroups; however, impact of low serum EPA on HF hospitali- zation was particularly prominent in male patients, and those with low high-density lipoprotein cholesterol or without statin. Conclusions: Low levels of serum n-3 PUFA were associated with lower HF-free survival in patients with AMI. YIA-CO-1 Effect of Exercise Training on Nitric Oxide Synthasesin the Cardiovasculature and Kidney of Rats with Chronic Heart Failure DAISUKE ITO 1 , OSAMU ITO 1 , NOBUYOSHI MORI 1 , CHIHIRO SUDA 1 , KIYOTAKA HAO 2 , PENG-YU CAO 1 , YOSHIKAZU MUROYA 1 , KENTA TAKASHIMA 1 , HIROAKI SHIMOKAWA 2 , MASAHIRO KOHZUKI 1 1 Department of Internal Medicine and Rehabilitation Science, Tohoku University, Sendai, Japan, 2 Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan Aims: Exercise training has beneficial effects in patients with heart disease, and is known to upregulate endothelial nitric oxide synthase (eNOS) in cardiovasculature. However, the effects of exercise training on nitric oxide synthase (NOS) in the kidney with heart disease have not been reported. Thus, the aim of the present study is to examine whether exercise training upregulates the NOS in the kidney and The 16 th Annual Scientific Meeting JHFS S147

Transcript of Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free...

Page 1: Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free Survival after Acute Myocardial Infarction

The 16th Annual Scientific Meeting � JHFS S147

YIA-CL-1Subcutaneous Tissue Biopsy is a Useful Diagnostic and Prognostic Tool forCardiac AmyloidosisYASUHIRO IZUMIYA, SEIJI TAKASHIO, MEGUMI YAMAMURO, SUNAOKOJIMA, HISAO OGAWADepartment of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan

Introduction: Cardiac involvement in systemic amyloidosis causes detrimental prog-nosis, therefore early detection and classification are important to develop appropri-ate therapeutic strategies. Subcutaneous tissue biopsy is a useful screening forsystemic amyloidosis; however, its diagnostic and prognostic value in patients withcardiac amyloidosis remains elusive. Methods: We retrospectively analyzed 14 con-secutive patients with cardiac amyloidosis who underwent subcutaneous tissue bi-opsy. Results: Amyloid deposition was observed in 11 patients (79%).Histopathological analysis demonstrated that acquired monoclonal immunoglobulinlight-chain amyloidosis could be predicted when the degree of amyloid depositionwas greater in blood vessels than adipose tissue compare to senile systemic amyloid-osis and familial amyloidosis (60% vs. 0%; p50.03). During the follow-up period(median 297 days, range 3-761 days), 7 patients died or were admitted to the hospitaldue to worsening heart failure. Among them, 6 patients (86%) were positive for am-yloid deposition in blood vessels. The incidence of death and composite outcome, in-cluding heart failure hospitalization and death, was significantly higher in patientspositive for amyloid deposition in blood vessels than in those without (p50.03,p50.006; respectively). Conclusions: Amyloid subtype could be diagnosed by ana-lyzing the degree of amyloid deposition in blood vessels and adipose tissue usingsubcutaneous tissue biopsy samples in patients with cardiac amyloidosis. Amyloiddeposition in blood vessels suggests poor prognosis of these patients.

YIA-CL-2Preoperative Levels of Bilirubin or Creatinine Adjusted by Age can PredictTheir Reversibility After Implantation of Left Ventricular Assist DeviceTERUHIKO IMAMURA1, KOICHIRO KINUGAWA2, TARO SHIGA1, TOSHIROINABA1, HISATAKA MAKI1, MASARU HATANO1, ATSUSHI YAO1, SHUNEIKYO2, MINORU ONO3, RYOZO NAGAI41Department of Cardiovascular Medicine, Graduate School of Medicine, Universityof Tokyo, Tokyo, Japan, 2Department of Therapeutic Strategy for Heart Failure,Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 3Department ofCardiothoracic Surgery, Graduate School of Medicine, University of Tokyo,Tokyo, Japan, 4Jichi Medical University, Tochigi, Japan

Background: To predict a reversibility of end-organ function after LVAD implanta-tion is difficult in patients with decompensated state, but is indispensable to determin-ing the eligibility for transplant listing. Methods and Results: Preoperative datawere obtained from 69 patients with LVAD (18 continuous-flow, 51 pulsatile). Persis-tent hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or cre-atinine (Cre) more than 1.5 mg/dL at 6 months after LVAD implantation. TB score orCre score was calculated: 0.15 � Age + 1.1 � (preoperative TB) or 0.2 � Age + 3.6� (preoperative Cre), in which coefficients were determined on the basis of odds ra-tios for persistent hepatic or renal dysfunction, respectively. ROC analyses showedgood predictabilities for persistent end-organ dysfunction (AUCs: 0.794 for the TBscore and 0.839 for the Cre score). Using the combination of both scores, 6 months’mortality by multiple organ failure was significantly stratified into 3 groups: the low(5.6%, the TB score !11.0 with any Cre score), intermediate (22.2%, the TB scoreO11.0 but the Cre score !14.1), and high (83.3%, the TB score O11.0 and the Crescore O14.1) risk strata. Conclusions: Reversibility of end-organ function withLVAD can be predicted by our new risk scoring system, which is beneficial in strat-ifying the likelihood of transplant listing during bridge to candidacy.

YIA-CL-3Cardiac Troponin T Release is Increased by Coronary MicrovascularDysfunction in Patients with Nonischemic Heart FailureSEIJI TAKASHIO, MEGUMI YAMAMURO, YASUHIRO IZUMIYA, SUNAOKOJIMA, HISAO OGAWADepartment of Cardiovascular Medicine, Graduate School of Medical Sciences,Kumamoto University, Kumamoto, Japan

Background: Cardiac troponin T (cTnT) is established as a specific biomarker of on-going myocardial damage and predicts adverse outcome in patients with heart failure(HF). However, the mechanisms of underlying cTnT release remain unclear. It is re-ported that coronary microvascular dysfunction is potential cause for elevated cTnTrelease. Therefore, we evaluated the association between coronary microvasculardysfunction and cTnT release from failing myocardium by novel highly sensitive as-say. Methods and Results: We studied 45 nonischemic HF patients (mean age:62615 y.o, Male: 69 %, ejection fraction: 42.5611.5 %). Coronary flow reserve(CFR) was calculated by using a intracoronary Doppler guidewire (FloWire, Volcano,Rancho Cordova, CA, U.S.A.) and CFR ! 2.0 was considered existing coronary mi-crovascular dysfunction. Serum cTnT levels sampled from aortic root (Ao) and cor-onary sinus (CS) simultaneously during cardiac catheterization were measured. cTnTextracted from heart was describe as the differences between Cs and Ao of cTnTlevels (d cTnT). CFR ! 2.0 was observed in 14 patients (31%). d cTnT levels of

CFR ! 2.0 patients were significantly higher than those of CFR O and 5 2.0 pa-tients (6.767.5 ng/L vs. 2.261.8 ng/L; p50.047). Conclusions: cTnT release intocoronary circulation was increased by existing coronary microvascular dysfunctionin nonischemic HF patients. Coronary microvascular dysfunction is considered oneof the causes for elevated cTnT.

YIA-CL-4Prognostic Impact of Increased Heart Rate on Heart Failure with PreservedEjection FractionTSUYOSHI TAKADA1, YASUHIKO SAKATA2, SATOSHI MIYATA2, JUNTAKAHASHI1, KOTARO NOCHIOKA1, MASANOBU MIURA1, HIROAKISHIMOKAWA1

1Department of Cardiovascular Medicine, Tohoku University Graduate School ofMedicine, Sendai, Japan, 2Department of Evidenced-Based CardiovascularMedicine, Tohoku University Graduate School of Medicine, Sendai, Japan

Background: Since heart failure (HF) with preserved ejection fraction (HFpEF) isgenerally complicated with diastolic dysfunction, it is anticipated that heart rate(HR) control is crucial for the management of HFpEF as compared with HF with re-duced EF (HFrEF). Thus, we examined the influence of HR control on cardiovascular(CV) mortality in patients with HFpEF and those with HFrEF. Methods: Among the10,219 patients in our cohort, as named CHART-2 Study, we enrolled 2,978 patientswith Stage C/D HF and sinus rhythm (mean age 67.8 years, 69.0% male). CV mor-tality during the median follow-up period of 3.1 years was compared among the fol-lowing 4 groups; G1 (n51121, HR!71bpm, EF$50%), G2 (n5853, HR$71bpm,EF$50%), G3 (n5491, HR!71bpm, EF!50%), and G4 (n5513, HR$71bpm,EF!50%). Results: G2 had a significantly higher CV mortality than G1 (6.0 vs.3.6%, P50.009), whereas G3 and G4 had similar CV mortality (10.0 vs. 9.9%,P50.740). A Cox regression analysis revealed that G2 was associated with signifi-cantly higher CV mortality than G1 (hazard ratio 1.79, P50.008), whereas G3showed comparable prognosis to G4 (hazard ratio 0.85, P50.418). Conclusions:These results indicate that increased HR is associated with worse prognosis in pa-tients with HFpEF but not in those with HFrEF, suggesting that HR could be a ther-apeutic target for HEpEF but not for HFrEF.

YIA-CL-5Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated withLower Heart Failure Free Survival after Acute Myocardial InfarctionMASAHIKO HARA1, YASUHIKO SAKATA1,2, SEN MATSUMOTO1, MASAYAUSAMI1, SHINICHIRO SUNA1, DAISAKU NAKATANI1, ISSEI KOMURO1

1Department of Cardiovascular Medicine, Osaka University Graduate School ofMedicine, Suita, Japan, 2Department of Cardiovascular Medicine and Departmentof Evidence-based Cardiovascular Medicine, Tohoku University Graduate Schoolof Medicine, Sendai, Japan

Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), in-cluding docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associatedwith a lower risk of atherosclerotic cardiovascular events, particularly acute myocar-dial infarction (AMI). However, limited data are available regarding the associationbetween serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI.Methods and Results: We evaluated whether serum DHA and EPA levels were as-sociated with HF-free survival, and HF hospitalization rates after AMI. We enrolled712 AMI patients and divided them into 3 groups (Low, Middle, and High) accordingto the tertile values of DHA or EPA serum levels. Impact of serum n-3 PUFA levelswas assessed using propensity-score-stratified Cox regression analysis. Althoughboth DHA and EPA Low groups showed statistically significant worse HF-free sur-vival as compared to other groups (HR 1.68, p50.0358 in DHA and HR 1.69,p50.0280 in EPA), only EPA Low group had a higher risk of HF hospitalization(HR 2.40, p50.0097). Unfavorable impacts of low DHA or EPA levels were gener-ally common in all subgroups; however, impact of low serum EPA on HF hospitali-zation was particularly prominent in male patients, and those with low high-densitylipoprotein cholesterol or without statin. Conclusions: Low levels of serum n-3PUFA were associated with lower HF-free survival in patients with AMI.

YIA-CO-1Effect of Exercise Training on Nitric Oxide Synthasesin the Cardiovasculatureand Kidney of Rats with Chronic Heart FailureDAISUKE ITO1, OSAMU ITO1, NOBUYOSHI MORI1, CHIHIRO SUDA1,KIYOTAKA HAO2, PENG-YU CAO1, YOSHIKAZU MUROYA1, KENTATAKASHIMA1, HIROAKI SHIMOKAWA2, MASAHIRO KOHZUKI11Department of Internal Medicine and Rehabilitation Science, Tohoku University,Sendai, Japan, 2Department of Cardiovascular Medicine, Tohoku University,Sendai, Japan

Aims: Exercise training has beneficial effects in patients with heart disease, and isknown to upregulate endothelial nitric oxide synthase (eNOS) in cardiovasculature.However, the effects of exercise training on nitric oxide synthase (NOS) in the kidneywith heart disease have not been reported. Thus, the aim of the present study is toexamine whether exercise training upregulates the NOS in the kidney and